N-fatty acid-amino acid conjugates and therapeutic uses

Abstract

The present invention relates to the use of N-fatty acid-amino acid conjugates to treat, prevent, or manage tissue inflammation, leukocyte adhesion, or pain. The invention includes pharmaceutical compositions comprising N-fatty acid-amino acid conjugates and methods of administering N-fatty acid-amino acid conjugates and pharmaceutical compositions thereof as therapeutic agents.

What is claimed is:  
     
         1 . A method of treating inflammation of bodily tissue of a subject, the method comprising administering to the subject an anti-inflammatory amount of an N-fatty acid-amino acid conjugate having the general formula:  
       
         
           
           
               
               
           
         
       
       wherein R 1  can be any one of myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, eicosatrienoic acid, arachidonic acid, eicosapentenoic acid, or docosatetraenoic acid; and R 2  can be any one of glycine, D-alanine, L-alanine, D-valine, L-valine, D-leucine, L-leucine, D-isoleucine, L-isoleucine, D-phenylalanine, L-phenylalanine, D-asparagine, L-asparagine, D-glutamine, L-glutamine, or γ-aminobutyric acid.  
     
     
         2 . The method of  claim 1 , wherein the anti-inflammatory amount of the N-fatty acid-amino acid conjugate is administered orally, topically, or subcutaneously.  
     
     
         3 . The method of  claim 1 , wherein the anti-inflammatory amount of the N-fatty acid-amino acid conjugate is administered in the form of a tablet or gelatin capsule.  
     
     
         4 . The method of  claim 1 , wherein the anti-inflammatory amount of the N-fatty acid-amino acid conjugate is administered mixed with DMSO.  
     
     
         5 . The method of  claim 1 , wherein the anti-inflammatory amount of the N-fatty acid-amino acid conjugate is a dosage of about 0.1-10 mg/kg of body weight per day.  
     
     
         6 . The method of  claim 1 , wherein the anti-inflammatory amount of the N-fatty acid-amino acid conjugate is a dosage of about 1.4-2.1 mg/kg of body weight per day.  
     
     
         7 . The method of  claim 1 , wherein the anti-inflammatory amount of the N-fatty acid-amino acid conjugate is a dosage of about 10-700 mg per day.  
     
     
         8 . The method of  claim 1 , wherein the anti-inflammatory amount of the N-fatty acid-amino acid conjugate is a dosage of about 100-150 mg per day.  
     
     
         9 . The method of  claim 1 , wherein the N-fatty acid-amino acid conjugate is N-arachidonylglycine.  
     
     
         10 . The method of  claim 1 , wherein R 2  is D-alanine, L-alanine, or γ-aminobutyric acid.  
     
     
         11 . A method of treating pain in a subject, the method comprising administering to the subject an analgesic amount of an N-fatty acid-amino acid conjugate having the general formula:  
       
         
           
           
               
               
           
         
       
       wherein R 1  can be any one of myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, eicosatrienoic acid, arachidonic acid, eicosapentenoic acid, or docosatetraenoic acid; and R 2  can be any one of D-alanine, L-alanine, D-valine, L-valine, D-leucine, L-leucine, D-isoleucine, L-isoleucine, D-phenylalanine, L-phenylalanine, D-asparagine, L-asparagine, D-glutamine, L-glutamine, or γ-aminobutyric acid.  
     
     
         12 . The method of  claim 11 , wherein the analgesic amount of the N-fatty acid-amino acid conjugate is administered orally, topically, or subcutaneously.  
     
     
         13 . The method of  claim 11 , wherein the analgesic amount of the N-fatty acid-amino acid conjugate is administered in the form of a tablet or gelatin capsule.  
     
     
         14 . The method of  claim 11 , wherein the analgesic amount of the N-fatty acid-amino acid conjugate is administered mixed with DMSO.  
     
     
         15 . The method of  claim 11 , wherein the analgesic amount of the N-fatty acid-amino acid conjugate is a dosage of about 0.1-10 mg/kg of body weight per day.  
     
     
         16 . The method of  claim 11 , wherein the analgesic amount of the N-fatty acid-amino acid conjugate is a dosage of about 1.4-2.1 mg/kg of body weight per day.  
     
     
         17 . The method of  claim 11 , wherein the analgesic amount of the N-fatty acid-amino acid conjugate is a dosage of about 10-700 mg per day.  
     
     
         18 . The method of  claim 11 , wherein the analgesic amount of the N-fatty acid-amino acid conjugate is a dosage of about 100-150 mg per day.  
     
     
         19 . The method of  claim 11 , wherein R 2  is D-alanine, L-alanine, or γ-aminobutyric acid.  
     
     
         20 . A pharmaceutical composition comprising an N-fatty acid-amino acid conjugate and a carrier for oral or topical administration, wherein said N-fatty acid-amino acid conjugate has the general formula  
       
         
           
           
               
               
           
         
       
       wherein R 1  can be any one of myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, eicosatrienoic acid, arachidonic acid, eicosapentenoic acid, or docosatetraenoic acid; and R 2  can be any one of glycine, D-alanine, L-alanine, D-valine, L-valine, D-leucine, L-leucine, D-isoleucine, L-isoleucine, D-phenylalanine, L-phenylalanine, D-asparagine, L-asparagine, D-glutamine, L-glutamine, or γ-aminobutyric acid.